chr16-89686761-T-G

Position:

• chr16-89686761-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PVS1_Strong BP6 BS1

The ENST00000505473.5(CDK10):​c.-127+2T>G variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000324 in 1,612,354 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00049 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00031 (1 hom.)
• Consequence: CDK10 ENST00000505473.5 splice_donor
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.216

Genes affected

CDK10 (HGNC:1770): (cyclin dependent kinase 10) The protein encoded by this gene belongs to the CDK subfamily of the Ser/Thr protein kinase family. The CDK subfamily members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and are known to be essential for cell cycle progression. This kinase has been shown to play a role in cellular proliferation and its function is limited to cell cycle G2-M phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

LINC02166 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.10866911 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.9, offset of 20, new splice context is: acgGTgcct. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• BP6: Variant 16-89686761-T-G is Benign according to our data. Variant chr16-89686761-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1027754.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000307 (448/1460330) while in subpopulation MID AF= 0.00954 (55/5766). AF 95% confidence interval is 0.00753. There are 1 homozygotes in gnomad4_exome. There are 223 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK10	NM_052988.5	c.51T>G	p.Arg17=	synonymous_variant	1/13	ENST00000353379.12
LINC02166	NR_184150.1	n.152A>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK10	ENST00000353379.12	c.51T>G	p.Arg17=	synonymous_variant	1/13	1	NM_052988.5	P1

Frequencies

GnomAD3 genomes AF: 0.000494 AC: 75 AN: 151906 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00442

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000601 AC: 147 AN: 244612 Hom.: 0 AF XY: 0.000562 AC XY: 75 AN XY: 133502

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00201

Gnomad ASJ exome AF: 0.000804

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000558

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000409

Gnomad OTH exome AF: 0.00134

GnomAD4 exome AF: 0.000307 AC: 448 AN: 1460330 Hom.: 1 Cov.: 31 AF XY: 0.000307 AC XY: 223 AN XY: 726472

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00202

Gnomad4 ASJ exome AF: 0.00127

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000627

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.000647

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152024 Hom.: 1 Cov.: 34 AF XY: 0.000592 AC XY: 44 AN XY: 74328

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000352 Hom.: 1

Bravo AF: 0.000642

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000416

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Al Kaissi syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Feb 07, 2020

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

CDK10: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201507040; hg19: chr16-89753169;